Heart failure represents the final common pathway of many risk factors and cardiovascular illnesses resulting in significant morbidity and mortality. The increase in heart failure rates throughout the world represents an enormous public health problem.
The number of cases and deaths attributable to heart failure has increased despite advances in treatment and a decline in other major cardiovascular diseases over the same interval. Currently more than 5.2 million patients in the United States have heart failure, and more than 550,000 are diagnosed annually. Heart failure leads to 12 to 15 million office visits and 6.5 million hospital days, and more than 57,000 patients die of heart failure as a primary cause annually.
Heart failure is primarily a condition of the elderly, and thus the widely recognized “aging of the population” also contributes to the increasing incidence of heart failure. The incidence of heart failure approaches 10 per 1000 population after age 65, and approximately 80% of patients hospitalized with heart failure are more than 65 years old. Heart failure is the most common Medicare diagnosis-related group (i.e., hospital discharge diagnosis), and more Medicare dollars are spent for the diagnosis and treatment of heart failure than for any other diagnosis. In addition, patients suffering from chronic congestive heart failure have a five-year mortality rate of approximately 50%.
Chronic congestive heart failure is characterized by a progressive loss in the heart's ability to pump blood. Different diseases can cause congestive heart failure, including coronary artery disease, heart attacks, inflammation of the heart tissue and diseases of the heart valves, and infection. Weakened heart muscle often results in poor cardiac output because the heart is unable to empty blood adequately from the ventricles to the circulation with each beat. Congestive heart failure symptoms include shortness of breath, edema, or fluid retention, and swelling of the legs and feet. Congestive heart failure symptoms that result from the inefficiency of the heart to distribute or adequately pump oxygen-rich blood to body tissues include fatigue and weakness as well as a loss of appetite. As the disease progresses, these symptoms can severely impact the patient's quality of life, so that even the ability to perform simple tasks, such as walking across the room, becomes limited. While some cardiac risk factors such as smoking, high cholesterol, high blood pressure, diabetes and obesity can be controlled with lifestyle changes, the majority of patients with CHF require additional treatments to help manage their disease.
Congestive heart failure is characterized as a syndrome rather than a disease, because of the complexity of its many causes and pathophysiological origins. For this reason, current medications for the treatment of CHF are sub-optimal; they include diuretics, inotropes, vasodilators and beta blockers, which generally focus on single components of the diverse pathways contributing to CHF. Diuretics help the kidneys rid the body of excess fluid, thereby reducing blood volume and the heart's workload. Inotropes strengthen the heart's pumping action. Vasodilators, such as ACE inhibitors, cause the peripheral arteries to dilate, making it easier for blood to flow. Beta blockers slow the heart rate and reduce blood pressure by blocking the effects of adrenaline.
Many congestive heart failure patients eventually experience a rapid deterioration and worsening of symptoms, or decompensation, despite continuing medical therapy and require urgent treatment in the hospital. This condition is called acute decompensated heart failure (ADHF or acute heart failure). The number of hospitalizations for worsening congestive heart failure have risen dramatically in the past 30 years from approximately 400,000 in 1979 to approximately 1.1 million in 2005. Acute heart failure is also the most frequent cause of hospitalization among Medicare patients.
Acutely decompensated heart failure resulting in hospitalization marks a fundamental change in the natural history of the progression of congestive heart failure. Reasons for this are unclear but may involve the intensification of existing pathophysiologic processes or entirely new ones, or it may reflect a deleterious effect of conventional treatments given to control worsening symptoms. Mortality rates in the year following hospitalization for acute heart failure patients are significantly higher than in non-hospitalized patients, and heart failure hospitalization remains one of the most important risk factors for mortality. Moreover, these patients are particularly prone to readmission, with recurrent hospitalization rates of 50% within 6 months of discharge.
Treatment strategies for ADHF have been largely empirical and limited by the complex pathophysiology of the syndrome which is not completely understood. Moreover, treatment strategies are complicated by the heterogeneity of clinical presentation among ADHF patients. Traditionally, heart failure has been associated with a reduced left ventricular ejection fraction (generally LVEF <35%) that defines patients with systolic dysfunction. However, over the past decade, there has been a growing recognition of a significant and growing group of acute heart failure patients with preserved LV ejection fraction characterized by diastolic dysfunction. This group of ADHF patients are believed to represent nearly one-half of all ADHF patients. A high proportion of patients with preserved LV ejection fraction are women and diabetics.
Standard treatment regimens for ADHF include diuretics, vasodilators, and inotropic agents to improve symptoms, but no treatment has been shown to improve outcomes (mortality and rehospitalization) of these patients. In fact, in some instances these therapies have been shown to worsen prognosis. Inotropic agents, for example, improve systolic function, as demonstrated by improving left ventricular ejection fraction, but do so by making the damaged heart work harder, as evidenced by increasing myocardial oxygen demand (MVO2), thereby contributing to worsening long-term outcomes.